Coumarin-Based Noncytotoxicity Fluorescent Dye for Tracking Actin Protein in In-Vivo Imaging.

shares maximum homology with the human disease-causing genes and thus has been employed to evaluate the toxicity of numerous compounds. Further, its distinguishable developmental stages, easy rearing, and short lifespan make it a perfect model organism to study toxicological properties of any new compound. The current study evaluates the toxic effect of a coumarin-based organic fluorescent dye, 7-hydroxy-4-methyl-8-((4-(2-oxo-2-chromen-3-yl)thiazol-2-ylimino)methyl)-2-chromen-2-one (), using as a model organism by studying different behavioral, screening, and staining techniques using flies.

N^N N^E (E = S or Se) coordination behavior of imino-phosphanamidinate chalcogenide ligands towards aluminum alkyls: efficient hydroboration catalysis of nitriles, alkynes, and alkenes.

The synthesis, characterization, and catalytic application of six aluminum alkyl complexes supported by various imino-phosphanamidinate chalcogenide ligands are described. Six different unsymmetrical imino-phosphanamidinate chalcogenide ligands [NHIP(Ph)(E)NH-Dipp] [R = 2,6-diisopropylphenyl (Dipp), E = S (2a-H), Se (2b-H); R = mesityl (Mes), E = S (3a-H), Se (3b-H); R = -butyl (Bu), E = S (4a-H), Se (4b-H)] were prepared by the oxidation of respective imino-phosphanamide ligands (1a, 1b and 1c) with elemental chalcogen atoms (S and Se). The aluminum complexes with imino-phosphanamidinate chalcogenide ligands with the general formulae [κ-{NHIP(Ph)(E)N-Dipp}AlMe] [R = Dipp, E = S (5a), Se (5b); R = Mes, E = S (6a), Se (6b)] or [κ-{NHIP(Ph)(E)N-Dipp}AlMe] [R = Bu, E = S (7a), Se (7b)] were synthesized in good yields from the reaction of the suitable protic ligands (2a,b-H-4a,b-H) and trimethylaluminum in a 1 : 1 molar ratio in toluene at room temperature.

Enzymatic Substrate Inhibition in Metal Free Catecholase Activity.

The catecholase activities were routinely modeled using transition metal complexes as catalyst and in some case basic pH were used as a reaction condition. In this article, the catalytic aerobic oxidation of proxy substrate 3,5-di-tert-butylcatechol (DTBC) in methanol using triethylamine/diethylamine as catalyst was demonstrated as a functional mimic of catecholase activity. The kinetic manifestation of DTBC oxidation was explained as enzymatic substrate inhibition pattern in Michaelis-Menten kinetic model.

Synthesis of First Coumarin Fluorescent Dye for Actin Visualization.

Selective fluorescence imaging of actin protein hugely depends on the fluorescently labeled actin-binding domain (ABD). Thus, it is always a challenging task to image the actin protein ( or ) directly with an ABD-free system. To overcome the limitations of actin imaging without an ABD, we have designed a facile and cost-effective red fluorescent coumarin dye 7-hydroxy-4-methyl-8-(4-(2-oxo-2-chromen-3-yl)thiazol-2-ylimino)methyl-2-chromen-2-one () for actin binding.

Oxygen Activation by a Copper Complex with Sulfur-Only Coordination Relevant to the Formylglycine Generating Enzyme.

Synthesizing hydrosulfido Cu thiolate complexes is quite challenging. In this report, two new and rare hydrosulfido Cu thiolate complexes, [EtN][(mnt)Cu-SH] (, mnt = maleonitrile dithiolene = SC(CN)) and [EtN][(mnt)Cu-(μ-SH)-Cu(mnt)] (), have been synthesized. Coordination sites and O activation by complex resemble the formylglycine generating enzyme (FGE), an enzyme recently crystallographically characterized with sulfur-only coordination around Cu (three thiolate ligands).

Strategic Substitution of -OH/-NR (R=Et, Me) Imparts Colorimetric Switching between F and Hg by Salicyaldehyde/Benzaldehyde-Quinoxaline Conjugates.

We herein report two salicyaldehyde-quinoxaline (HQS and HQSN) conjugates and a benzaldehyde-quinoxaline (QBN) conjugate to fabricate selective chemosensors for F and Hg in the micromolar range. This work demonstrates how sensing outcomes are affected by modulating proton acidity by introducing an electron donating group, -NEt , in the probe backbone. Interestingly, the un-substituted probe HQS can selectively detect F , whereas HQSN and QBN are selective for Hg .

FeO coated guargum nanoparticles as non-genotoxic materials for biological application.

The current study aims to check various behavioural, developmental, cytotoxic, and genotoxic effects of FeO-GG nanocomposite (GGNCs) on Drosophila melanogaster. FeO nanoparticles were prepared by the chemical co-precipitation method and cross-linked with guargum nanoparticles to prepare the nanocomposites. The nanocomposites were characterized by using transmission electron microscopy (TEM), X-ray diffraction (XRD), and FTIR techniques.

Environmental cue affects the hearing-related behaviors of Drosophila melanogaster by targeting the redox pathways.

Environmental cues like noise, pressure, and circadian rhythm can affect the hearing ability of human beings. Nevertheless, the complex physiology of the human being does not allow us to understand how these factors can affect hearing and hearing-related behaviors. Conversely, these effects can be easily checked using the hearing organ of Drosophila melanogaster, the Johnston organ.

Assessing the potential of lignin nanoparticles as drug carrier: Synthesis, cytotoxicity and genotoxicity studies.

Lignin nanoparticles synthesis is among recent developments in lignin valorization especially for biomedical applications. In this study, a new technique where complete self-assembling of lignin was ensured by simultaneous solvent displacement and flash pH change was used to optimize particle size of blank lignin nanoparticles (BLNPs) for suitability in cell uptake along with maximized yield. To establish BLNPs as drug carrier, safety studies including hemocompatibility, cytotoxicity and elaborate genotoxicity studies on Drosophila melanogaster as a model organism were done.

Metal Ion (Ni vs Co)-Mediated Unusual Amine-Imine Interconversion in Conjugated Amine-ene-imine Ligand: Synthesis, Structure, and Characterization.

Two configurationally isomeric ligands, namely, 2-(()-benzylideneamino)-3-((pyridin-2-ylmethyl)amino)maleonitrile () and 2-(benzylamino)-3-(()-(pyridin-2-ylmethylene)amino)maleonitrile (), were synthesized and fully characterized, which are malenonitrile-tethered, N atom donors tridentate ligands. Structurally, they differ in the interchangeable position of amine and imine group only. Under the same reaction condition, Ni(II) invoked the transformation of (L) to (L) via simultaneous oxidation of amine to imine and the reduction of imine to amine.

A quinoxaline-diaminomaleonitrile conjugate system for colorimetric detection of Cu in 100% aqueous medium: observation of aldehyde to acid transformation.

In this work, we have strategically incorporated a quinoxaline derivative and a diaminomaleonitrile moiety to construct a chemosensor, 2-amino-3-[(quinoxalin-2-ylmethylene)-amino]-but-2-enedinitrile (H2qm). The notable feature of this strategy is to generate a highly conjugated Schiff base platform with interesting binding properties. Remarkably, H2qm exhibited a visual sensing ability towards Cu2+ in 100% aqueous medium.

Translation attenuation via 3' terminal codon usage in bovine csn1s2 is responsible for the difference in αs2- and β-casein profile in milk.

The rate of secretion of αs2-casein into bovine milk is approximately 25% of that of β-casein, yet mammary expression of their respective mRNA transcripts (csn1s2 and csn2) is not different. Our objective was to identify molecular mechanisms that explain the difference in translation efficiency between csn1s2 and csn2. Cell-free translational efficiency of csn2 was 5 times that of csn1s2.

Enhanced translation of mRNAs encoding proteins involved in mRNA translation during recovery from heat shock.

Unlabelled: The mRNAs encoding poly (A) binding protein (PABP1), eukaryotic elongation factor 1A (eEF1A) and ribosomal protein S6 (RPS6) belong to the family of terminal oligo pyrimidine tract (TOP) containing mRNAs. Translation of the TOP mRNAs is regulated by growth signals and usually codes for proteins involved in mRNA translation. Previous studies from our laboratory showed that translation of PABP1 mRNA was preferentially enhanced during recovery of HeLa cells from heat shock.

Depletion of nuclear poly(A) binding protein PABPN1 produces a compensatory response by cytoplasmic PABP4 and PABP5 in cultured human cells.

Background: In vertebrates, poly(A) binding protein (PABP) is known to exist in five different isoforms. PABPs are primarily cytosolic with the exception of the nuclear PABP (PABPN1), which is located in the nucleus. Within the nucleus, PABPN1 is believed to bind to the poly(A) tail of nascent mRNA and along with cleavage and polyadenylation specificity factor (CPSF) define the length of the newly synthesized poly(A) tail.

Effect of high-dose oral rabeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

Background. The aim of this study was to compare the effect of high-dose oral rabeprazole versus high-dose IV PPI on rebleeding after endoscopic treatment of bleeding peptic ulcers. Methods.

Expression of the polyalanine expansion mutant of nuclear poly(A)-binding protein induces apoptosis via the p53 pathway.

The PABPN1 [nuclear poly(A)-binding protein 1] is ubiquitous, binds to the nascent mRNA transcript and controls the poly(A) tract elongation process in multicellular organisms. Expansion of GCG repeats that encode first 6 of the 10 alanine residues of a polyalanine tract at the N-terminus of wild-type PABPN1 to 12-17 alanine residues causes aggregation of the protein and cell death. Patients with the adult onset autosomal dominant OPMD (oculopharyngeal muscular dystrophy) carry the GCG expansion mutation in their PABPN1 gene.

In the absence of cellular poly (A) binding protein, the glycolytic enzyme GAPDH translocated to the cell nucleus and activated the GAPDH mediated apoptotic pathway by enhancing acetylation and serine 46 phosphorylation of p53.

The cytoplasmic poly (A) binding protein (PABP) interacts with 3' poly (A) tract of eukaryotic mRNA and is important for both translation and stability of mRNA. Previously, we have shown that depletion of PABP by siRNA prevents protein synthesis and consequently leads to cell death through apoptosis. In the present investigation, we studied the mechanism of cell apoptosis.

Depletion of cellular poly (A) binding protein prevents protein synthesis and leads to apoptosis in HeLa cells.

The cytoplasmic poly (A) binding protein (PABP) is important in mRNA translation and stability. In yeast, depletion of PABP leads to translation arrest. Similarly, the PABP gene in Drosophila is important for proper development.

Multiple levels of post-transcriptional control of expression of the poly (A)-binding protein.

Regulation of gene expression at the post-transcriptional level such as control of mRNA translation and stability is of fundamental importance because it allows cells to respond quickly to external signals, and change protein synthesis without new transcriptional activity. As such, control of translation and stability of mRNA play crucial roles in a variety of cellular processes, including regulating normal cellular growth, embryogenesis and neuronal plasticity. Consequently, misregulation of mRNA translation or degradation can be associated with a number of human diseases, such as cancer and diabetes.

Expression of poly(A)-binding protein is upregulated during recovery from heat shock in HeLa cells.

Induction of heat shock proteins (HSPs) helps cells to survive severe hyperthermal stress and removes toxic unfolded proteins. At the same time, the cap-dependent translation of global cellular mRNA is inhibited, due to the loss of function of eukaryotic initiation factor (eIF)4F complex. It has been previously reported that, following heat shock, HSP27 binds to the insoluble granules of eIF4G and impedes its association with cytoplasmic poly(A)-binding protein (PABP) 1 and eIF4E.

Induction of expression and co-localization of heat shock polypeptides with the polyalanine expansion mutant of poly(A)-binding protein N1 after chemical stress.

Formation of nuclear inclusions consisting of aggregates of a polyalanine expansion mutant of nuclear poly(A)-binding protein (PABPN1) is the hallmark of oculopharyngeal muscular dystrophy (OPMD). OPMD is a late onset autosomal dominant disease. Patients with this disorder exhibit progressive swallowing difficulty and drooping of their eye lids, which starts around the age of 50.

IMP1 interacts with poly(A)-binding protein (PABP) and the autoregulatory translational control element of PABP-mRNA through the KH III-IV domain.

Repression of poly(A)-binding protein (PABP) mRNA translation involves the formation of a heterotrimeric ribonucleoprotein complex by the binding of PABP, insulin-like growth factor II mRNA binding protein-1 (IMP1) and the unr gene encoded polypeptide (UNR) to the adenine-rich autoregulatory sequence (ARS) located at the 5' untranslated region of the PABP-mRNA. In this report, we have further characterized the interaction between PABP and IMP1 with the ARS at the molecular level. The dissociation constants of PABP and IMP1 for binding to the ARS RNA were determined to be 2.

Ectopic expression of a polyalanine expansion mutant of poly(A)-binding protein N1 in muscle cells in culture inhibits myogenesis.

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset dominant genetic disease caused by the expansion of a GCG trinucleotide repeat that encodes the polyalanine tract at the N-terminus of the nuclear poly(A)-binding protein (PABPN1). Presence of intranuclear inclusions (INIs) containing PABPN1 aggregates in the skeletal muscles is the hallmark of OPMD. Here, we show that ectopic expression of the mutant PABPN1 produced INIs in a muscle cell culture model and reduced expression of several muscle-specific proteins including alpha-actin, slow troponin C, muscle creatine kinase, and two myogenic transcription factors, myogenin and MyoD.

The autoregulatory translational control element of poly(A)-binding protein mRNA forms a heteromeric ribonucleoprotein complex.

Repression of poly(A)-binding protein (PABP) mRNA translation involves the binding of PABP to the adenine-rich autoregulatory sequence (ARS) in the 5'-untranslated region of its own mRNA. In this report, we show that the ARS forms a complex in vitro with PABP, and two additional polypeptides of 63 and 105 kDa. The 63 and 105 kDa polypeptides were identified, as IMP1, an ortholog of chicken zip-code binding polypeptide, and UNR, a PABP binding polypeptide, respectively, by mass spectrometry of the ARS RNA affinity purified samples.